MANIPULATION OF SUBSTITUENTS AT NITROGEN IN TROPANES, HOMOTROPANES, AND DEHYDRO-DERIVATIVES

Trop-6-ene (8-methyl-8-azabicyclo[3.2.1]oct-6-ene) and substituted N-b enzylnortrop-6-enes are synthesised. N-Debenzylation of tropanes fails using a wide variety of non-hydrogenolytic conditions despite effecti ve application in model piperidine derivatives; debenzylation of homot ropanes is more successful, giving norhomotropane and norhomotrop-7-en e. Bridged N-benzyl compounds react more slowly than N-methyl analogue s with chloroformates; the resulting quaternary intermediates are more prone than the N-methyl analogues to suffer competitive reversion to the starting amine, especially in the tropanes, consistent with slower S(N)2 attack at the benzylic carbon during decomposition; the use of an N-p-methoxybenzyl group does allow partial debenzylation to nortrop -6-ene, suggesting greater SNI character in the decomposition step in this case. 'Equatorial' attack is preferred in methylation of N-benzyl -nortrop-6-ene and -homotrop-7-ene with CH3I; subsequent reductive deb enzylation of the quaternary salt achieves overall replacement of N-be nzyl by N-methyl in both cases. VT NMR studies show the presence of a single 'equatorial' invertomer (Cl syn- to the 2C-bridge) in N-chloro- norhomotropanes and -7-enes and, by analogy, in the N-alkyl compounds. (C) 1998 Elsevier Science Ltd. All rights reserved.